Lithium hydroxide, monohydrate → (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-proline

HRID 475340Notes

Reaction equation

HRID 475340 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)[C:10]([N:12]1[C@@H:20]([C:21]#[C:22][Si](C)(C)C)[CH2:19][CH2:18][C@H:13]1[C:14]([O:16]C)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>CO.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:27]1[CH2:28][CH2:29][CH2:30][CH2:31]1)[C:10]([N:12]1[C@@H:20]([C:21]#[CH:22])[CH2:19][CH2:18][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66756897methyl (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-((trimethylsilyl)ethynyl)-L-prolinate

Product 1

HCID 86592934(5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-proline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of methyl (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-((trimethylsilyl)ethynyl)-L-prolinate (1.65 g, 3.66 mmol) in MeOH (10 mL) and H2O (10 mL) at room temperature was added LiOH.H2O (0.23 g, 5.49 mmol). The reaction mixture was stirred at room temperature for 16 hours and concentrated under reduced pressure. The residue was taken up in water and extracted with diethyl ether (2×). The aqueous layer was acidified to pH˜4 by adding 4% KHSO4 dropwise. The clear solution was extracted with ethyl acetate (3×) and the combined ethyl acetate layers were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to provide the titled compound. MS (CI) m/e 365 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionextracted with diethyl ether (2×)
  3. additionby adding 4% KHSO4 dropwise
  4. extractionThe clear solution was extracted with ethyl acetate (3×)
  5. washthe combined ethyl acetate layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f12dc94a50434dcf9bf1dd69b49db3b6
Source dataset
uspto-grants-2014_01
Patent number
US08637546B2

Reaction notes

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